Metabolomic profiling of ascending thoracic aortic aneurysms and dissections - Implications for pathophysiology and biomarker discovery

Doppler,C.;Arnhard,K.;Dumfarth,J.;Heinz,K.;Messner,B.;Stern,C.;Koal,T.;Klavins,K.;Danzl,K.;Pitterl,F.;Grimm,M.;Oberacher,H.;Bernhard,D.;
OBJECTIVE: Our basic understanding of ascending thoracic aortic aneurysm (ATAA) pathogenesis is still very limited, hampering early diagnosis, risk prediction, and development of treatment options. "Omics"-technologies, ideal to reveal tissue alterations from the normal physiological state due to disease have hardly been applied in the field. Using a metabolomic approach, with this study the authors seek to define tissue differences between controls and various forms of ATAAs. METHODS: Using a targeted FIA-MS/MS metabolomics approach, we analysed and compared the metabolic profiles of ascending thoracic aortic wall tissue of age-matched controls (n = 8), bicuspid aortic valve-associated aneurysms (BAV-A; n = 9), tricuspid aortic valve-associated aneurysms (TAV-A; n = 14), and tricuspid aortic valve-associated aortic dissections (TAV-Diss; n = 6). RESULTS: With sphingomyelin (SM) (OH) C22:2, SM C18:1, SM C22:1, and SM C24:1 only 4 out of 92 detectable metabolites differed significantly between controls and BAV-A samples. Between controls and TAV-Diss samples only phosphatidylcholine (PC) ae C32:1 differed. Importantly, our analyses revealed a general increase in the amount of total sphingomyelin levels in BAV-A and TAV-Diss samples compared to controls. CONCLUSIONS: Significantly increased levels of sphingomyelins in BAV-A and TAV-Diss samples compared to controls may argue for a repression of sphingomyelinase activity and the sphingomyelinase-ceramide pathway, which may result in an inhibition of tissue regeneration; a potential basis for disease initiation and progression.
PLoS One 2017 12:e0176727
Tags: Adult; Aged; Amino Acids/analysis; Aneurysm, Dissecting/metabolism/physiopathology; Aorta, Thoracic/chemistry; Aortic Aneurysm, Thoracic/metabolism/physiopathology; Biomarkers/analysis; Carnitine/analogs & derivatives/chemistry; Case-Control Studies; Ceramides/analysis; Female; Hexoses/chemistry; Humans; Lysophosphatidylcholines/analysis; Male; Metabolomics; Middle Aged; Phosphatidylcholines/analysis; Sphingomyelins/analysis; Young Adult;
PubMed: 28467501
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